Early onset of drug use in adolescence, especially alcohol and tobacco, has been repeatedly linked to later symptoms of SUD. In addition, use of alcohol during adolescence has been linked to impairment of cognitive function, especially working memory ability (WMA). These findings suggest that intervention to prevent the initiation of drug use during early adolescence could help to avert many of the adverse consequences of drug use, including not only SUD but also impairment of WMA. Despite this evidence, the mechanisms underlying the effects of early onset remain unclear. The present research aims to clarify those mechanisms so that firmer implications for prevention can be drawn. In particular, previous research has been based primarily on cross- sectional studies of adults with retrospective reports of drug use during adolescence. This research cannot determine whether early initiation of drug use includes mere experimentation with drugs or only the early progression of drug use. The early onset hypothesis would predict that early progression is the more critical factor for later adverse outcomes. In addition, previous research suggests that early drug use is merely a marker for more general pre-existing vulnerabilities that increase the risks of those outcomes in later adolescence and adulthood. The present research aims to provide a test of these competing hypotheses by conducting a follow-up study of a longitudinal-cohort of Philadelphia adolescents (N=387) that started at ages 10-12 and that were assessed annually for 5 years by our team of researchers. The Philadelphia Trajectory Study (PTS) has longitudinal data on WMA as well as different forms of impulsivity that indicate that early use of drugs, whether it leads to progression or not, is related to impulsive tendencies that reflect weakness in WMA. The PTS suggests that WMA and associated forms of impulsivity are the underlying risk factors for later adverse drug effects rather than early initiation per se. If this hypothesis were confirmed, it would suggest that early WMA training might be a valuable prevention strategy to prevent the adverse effects of drugs. The proposed study with a single follow-up assessment of the PTS when the cohort will be in an age range of high drug-use initiation and risk for SUD (18-19) can determine whether early vulnerabilities for drug use can explain differences in early experimentation vs. progression in drug use as well as later initiatio for symptoms of SUD (Aim 1). It can also determine whether early weakness in WMA and associated forms of impulsivity remain as risk factors for potential impairment in WMA linked to later drug use (Aim 2). Finally, it can determine whether other adverse outcomes apart from drug use are traceable to early weakness in WMA, such as problem gambling, anti-social behavior, sexual risks, and poor academic performance (Aim 3). PUBLIC HEALTH RELEVANCE: Disorders resulting from drug use are a major source of disability and mortality in the U.S. Initiation of drug use, especially alcohol and tobacco, prior o age 15 has been more strongly linked to the emergence of those disorders than initiation that occurs later in life. Understanding the mechanism linking early drug use with later adverse outcomes has important implications for strategies to prevent those outcomes. The present research will test two competing explanations for this association that can help to identify prevention strategies for the adverse effects of drug use.